Noropsikiyatri 2011-2 sirali

Aripiprazole-Induced Enuresis in a Child with Autistic Disorder
Otizm Tan›l› Bir Çocukta Aripiprazole Ba¤l› Enürezis
Hasan BOZKURT, Osman ABALI ‹stanbul Üniversitesi ‹stanbul T›p Fakültesi, Çocuk Ruh Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, ‹stanbul, Türkiye
ABSTRACTÖZET
Aripiprazole is being increasingly reported to be effective in treating behavioral
Aripiprazolün otistik çocuklarda görülen davran›ﬂsal problemleri tedavi etmede
problems of children with autism. It has fewer side effects with respect to other
etkili olmas›yla ilgili yay›nlar›n say›s› giderek artmaktad›r. Aripiprazolün di¤er
atypical antipsychotics. However, to our knowledge, in the literature, there is no
atipik antipsikotiklere nazaran daha az yan etkisi bulunmaktad›r. Oral aripiprazol
report on aripiprazole-induced enuresis in children and adolescents diagnosed
henüz piyasaya sürülmeden önce yap›lan de¤erlendirmelerde enürezis çok nadir
with autism, although enuresis has been a very rare adverse event observed dur-
bir yan etki olarak gözlenmesine ra¤men, bilindi¤i kadar›yla yaz›nda, otizm tan›l›
ing the premarketing evaluation of oral aripiprazole. Here, we present a sixteen-
çocuk ve ergenlerde aripiprazole ba¤l› enürezis ile ilgili bir vaka bildirimi yoktur.
year-old boy with diagnosis of autism and epilepsy who developed enuresis after
Biz bu yaz›da on alt› yaﬂ›nda otizm ve epilepsi tan›s› ile takip etti¤imiz, aripiprazole
starting aripiprazole and had rapid remission after the discontinuation of the
baﬂlad›ktan sonra enürezisi olan ve ilac› kestikten sonra alt kaç›rmas› h›zla düze-
drug. (Archives of Neuropsychiatry 2011; 48: 164-6)
len bir olgu sunduk.(Nöropsikiyatri Arﬂivi 2011; 48: 164-6)Key words: Aripiprazole, enuresis, autism, childrenAnahtar kelimeler: Aripiprazol, enürezis, otizm, çocukIntroductionCase Report
Aripiprazole anovel atypical antipsychotic, is being adminis-
H, a nonverbal 16-year-old male, was brought to our
tered to children and adolescents for the management of mood
outpatient clinic by his parents due to his aggressiveness and
instability, aggression, and psychosis. Recently, the U.S. Food
self-injurious behaviors. Information regarding his developmental
and Drug Administration (FDA) has approved it for the treatment
and psychiatric history was taken from his mother. According to
of irritability associated with autistic disorder in pediatric
her, he was diagnosed with autistic disorder due to his severe
patients aged 6-17 years and including symptoms of aggression
impairment in language development and social-emotional
towards others, deliberate self-injuriousness, temper tantrums,
reciprocity, and repetitive behaviors when he was 3. His medical
and quickly changing moods (1). Compared to other atypical
history was also positive for epilepsy. He was on valproic acid
antipsychotics, aripiprazole is reported to cause fewer side
2000 mg/day and lamotrigine 100 mg/day since the age of 12.
effects e.g., weight gain, elevation in glucose and lipid levels,
Risperidone was initiated at 0.5 mg/day to cope with his
prolactin elevation, QTc prolongation, and onset of diabetes
behavioral problems, but ceased because of excessive vomiting
mellitus. Other untoward events include headache, insomnia,
and gastrointestinal problems. Thus, we switched to olanzapine
nausea, vomiting, lightheadedness, somnolence, constipation,
5 mg/day. However, he began to have epileptic seizures soon
increased appetite and dyspepsia (2). Here, we present a case of
after olanzapine treatment, so the medication was stopped.
aripiprazole-induced enuresis in an adolescent with autistic
Then, he was given quetiapine, haloperidol and escitalopram,
respectively, but all these drugs also induced epilepsy by
Address for Correspondence/Yaz›ﬂma Adresi: Dr. Hasan Bozkurt, ‹stanbul Üniversitesi ‹stanbul T›p Fakültesi, Çocuk Ruh Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, ‹stanbul, Türkiye
Gsm: +90 554 237 19 32 E-mail: [email protected]Received/Geliﬂ tarihi: 05.09.2010 Accepted/Kabul tarihi: 31.10.2010
Archives of Neuropsychiatry, published by Galenos Publishing. / Nöropsikiyatri Arﬂivi Dergisi, Galenos Yay›nevi taraf›ndan bas›lm›ﬂt›r.Archives of Neuropsychiatry 2011; 48: 164-6Nöropsikiyatri Arﬂivi 2011; 48: 164-6
Aripiprazole-Induced Enuresis in an Adolescent with Autistic Disorder
decreasing the seizure threshold. Hence, we decided to
although it had no noticeable anticholinergic effects. As
use aripiprazole to control the symptoms and he was given
serotonin can indirectly potentiate cholinergic neuromuscular
aripiprazole 10 mg/day. But, he developed new-onset diurnal
transmission in isolated human detrusor muscle strips (10) and
enuresis within the first day of the treatment and it continued
there are a number of case reports on SSRI-induced enuresis
10-15 times a day till we stopped the medication a week later. His
(11-14), aripiprazole may be responsible for enuresis because of
medical history and workup, including physical and neurological
its serotonin reuptake properties (SERT). Besides, possible
examination and urinalysis, were unremarkable. The patient had
reduced dopamine transmission due to partial agonist activity of
urinary bladder control at 3 years of age, and he and his family
aripiprazole at D2 receptors might also cause urinary
had no previous history of urinary incontinence. His enuresis
incontinence in our autistic case despite the fact that the other
resolved rapidly after discontinuation of aripiprazole. We then
partial agonist activity at 5-HT1A receptors can reduce bladder
decided to restart aripiprazole to understand whether the diurnal
dysfunction, while selective 5-HT1A antagonists inhibit bladder
enuresis was associated with the use of aripiprazole or not.
Enuresis reemerged on the first day of the treatment and repeated
On the other hand, aripiprazole had no clinically important
10-15 times a day again. Meanwhile, he benefited from
interactions with the drugs, valproic acid and lamotrigine, which
aripiprazole and his behavioral symptoms resolved substantially
our patient was using (2). Because enuresis remitted rapidly
without emerging an epileptic seizure, but we could not keep upthe treatment because his parents requested the discontinua-
after discontinuation of aripiprazole and reemerged after
tion of aripiprazole due to the severity of enuresis, thus, we
starting again, the improvement of enuresis in this case cannot
ceased aripiprazole a week after the beginning and decided to
be explained by the other drugs. Our patient was using these
antiepileptics for four years and there was no dose increase thatmay contribute to the emergence of enuresis. Moreover, the risk
Discussion
of seizures with aripiprazole is reported to be 0.1%, the lowestamong atypical agents (1,2).
We reported the case of an autistic patient who developed
It is known that antipsychotic-induced enuresis happens to
diurnal enuresis after starting aripiprazole and had rapid
be mostly a transient and time-limited phenomenon (16,17). As
remission after the discontinuation of the drug. Although
our case had severe behavioral problems and communicational
antipsychotic-induced enuresis may be more common than
difficulties and his parents did not cope with the severity of
generally reported (3), urinary incontinence associated with
enuresis, we could not apply behavioral treatment and could not
aripiprazole has been a very rare adverse event observed during
the premarketing evaluation of its oral form.
Urinary incontinence associated with aripiprazole seems to
Possible mechanisms have been described in the
be very rare like the other cases with antipsychotic-induced
pathophysiology of antipsychotic-induced enuresis. They
enuresis (18) and our autistic case is probably the first report
include decreased internal bladder sphincter tone due to alfa 1
according to litereture (PubMed). Additionally, there are
adrenergic blockade (4), reduced dopamine transmission in the
two case reports describing the efficacy of combined use of
basal ganglia (5), urinary retention and subsequent overflow
aripiprazole in the treatment of clozapine-induced enuresis (19).
incontinence due to antimuscarinic properties of antipsychotics
However, the use of aripiprazole has become widely
(6) and blockade of pudendal reflexes via antagonism of 5-HT2 or
common in treating behavioral problems associated with
3 (7) and the activation of neuronal 5 HT4 receptors in the
autistic spectrum disorders; thus, our case report shows that
detrusor muscle (8). The sedative effects of antipsychotics may
aripiprazole-induced enuresis should be born in mind when
also lead to inability to wake up during sleep and might cause
using this drug especially in children with developmental
Moreover, efficacy of aripiprazole is mediated through a
disabilities. However, further research is needed to better
combination of partial agonist activity at D2 and 5-HT1A
understand the pathophysiology of enuresis with aripiprazole.
receptors and antagonist activity at 5-HT2A receptors. Actionsat receptors other than D2, 5-HT1A, and 5-HT2A may explain
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